In this paper, I argue that major elements of Hume’s metaphysics and epistemology are not only directed at the inductive argument from design which seemed to follow from the success of Newton’s system, but also have far larger aims. They are directed against the authority of Newton’s natural philosophy; the claims of natural philosophy are constrained by philosophic considerations. Once one understands this, Hume’s high ambitions for a refashioned ‘true metaphysics’ or ‘first philosophy’, that is, Hume’s ‘Science of Human Nature’, can be seen and evaluated in their proper light. Hume has three motives for his attack on Newton: his work is informed by and gives cover to superstitious beliefs; his project is not useful to the public; and its success generates a challenge to the independent authority of philosophy. This essay consists of five sections. First, I discuss Hume’s attitude toward Newton. Newton claims that natural philosophy should be the foundation for other sciences, while in the ‘Introduction’ to the Treatise Hume asserts the supremacy of the ‘science of man’. For Hume the human sciences can attain the high epistemic status of ‘proof’, while much of the physical sciences must do with lower forms of ‘probability’. Furthermore, Hume’s ‘rules by which to judge of causes and effects’ do not replicate Newton’s fourth Rule; this opens a gap between the ontologies and methodologies of Newton and Hume. Moreover, Hume’s account of causation is designed to undercut the reductionist bias of natural philosophy. According to Hume the parts of natural sciences that go beyond common life can be evaluated from the point of view of the science of man. I end with remarks on the philosophic origins and significance of Hume’s attack on Newton’s natural philosophy. I depart from two independent traditions of interpreting Hume. One tradition makes many references to Newton’s influence on Hume. On a more detailed level, proponents of this view may call attention to Hume’s ‘rules’, his ‘Experiments’ and ‘Anatomy’, his method of investigation, the application of Newtonian metaphors works (e.g., an ‘attraction’ in the ‘mental world’ on a par with that in the ‘natural world’ – the principles of association are, then, analogous to the laws of motion). Hume’s ‘science of man’ is said to be inspired by Newton’s science of nature. Hume wants his readers to feel that he is modeling his project on the successes of natural philosophy, exemplified by Newton. In the ‘Introduction’ to the Treatise and more explicitly in the opening pages of EHU, Hume suggests that his ‘science of man’ can parallel recent achievements in natural philosophy (especially planetary astronomy). Thus, my claim is not that Newton did not figure importantly in Hume’s philosophy, but, instead, that Hume’s project is in many respects more hostile to Newton’s achievements – as available to well-informed eighteenth-century readers – than many recent interpreters have realized. There is a different tradition that argues Hume simply did not understand Newton. Hume’s philosophy, thus, cannot do justice to Newtonian science. Hume’s lack of mathematical competence is said to be a barrier to his understanding of Newton’s mathematical natural philosophy. One finds this attitude behind the cranking of Bayesian machinery in John Earman’s attack on Hume’s treatment ‘Of Miracles’. However, this tradition begs the question; it takes the authority of ‘science’ for granted in Hume. Against this second tradition I argue that Hume did understand salient features of Newton’s methodology and position, although in ways often unappreciated by the first tradition mentioned above. For example, in his comments on Newton in the History of England, Hume discerns the (broad) outlines of Newton’s commitment to the method of analysis and synthesis (see Newton’s Opticks, Query 31) and how it differs from Boyle’s methodology. So, Hume has a subtle understanding of Newton’s methodology – even if one were to grant that he lacks appreciation of the role of mathematics in Newton’s natural philosophy. Leaving open the question whether Hume understood all the details of Newton’s system, Hume’s departures from Newton are best interpreted not as ‘ironic’, but as philosophically motivated.